Gabriela Fragiadakis, PhD

Assistant Professor

Medicine

I lead a computational immunology lab studying states of the human immune system across disease contexts using single-cell methods and data integration. We work with a variety of data types, including bulk- and single-cell sequencing and CyTOF. My research program is built from a foundation of collaborations as Director of the Data Science CoLab. Through CoLabs I have established partnerships to study systems-level immunity in viral infection, cancer, autoimmunity, and steady-state. From these projects I then pursue questions in immune phenotypes across contexts using high-dimensional analysis, data integration, and novel computational methods. In addition, I study immune-microbiome interactions at steady-state and in response to perturbation.

In the lab we have a sub-team that builds and develops the UCSF Data Library project, a web-based platform to store, curate, share and analyze high-dimensional data.

Publications:

Single-cell and spatial multi-omics highlight effects of anti-integrin therapy across cellular compartments in ulcerative colitis.

Nature communications

Mennillo E, Kim YJ, Lee G, Rusu I, Patel RK, Dorman LC, Flynn E, Li S, Bain JL, Andersen C, Rao A, Tamaki S, Tsui J, Shen A, Lotstein ML, Rahim M, Naser M, Bernard-Vazquez F, Eckalbar W, Cho SJ, Beck K, El-Nachef N, Lewin S, Selvig DR, Terdiman JP, Mahadevan U, Oh DY, Fragiadakis GK, Pisco A, Combes AJ, Kattah MG

Single-cell and spatial multi-omics identify innate and stromal modules targeted by anti-integrin therapy in ulcerative colitis.

bioRxiv : the preprint server for biology

Mennillo E, Kim YJ, Rusu I, Lee G, Dorman LC, Bernard-Vazquez F, Bain JL, Patel R, Andersen C, Rao A, Tamaki S, Tsui J, Shen A, Naser M, Eckalbar W, Cho SJ, Beck K, El-Nachef N, Lewin S, Selvig DR, Terdiman JP, Mahadevan U, Oh DY, Fragiadakis GK, Pisco A, Combes AJ, Kattah MG

Cell-Specific Transposable Element Gene Expression Analysis Identifies Associations with Systemic Lupus Erythematosus Phenotypes.

bioRxiv : the preprint server for biology

Cutts Z, Patterson S, Maliskova L, Taylor KE, Ye C, Dall'Era M, Yazdany J, Criswell L, Fragiadakis GK, Langelier C, Capra JA, Sirota M, Lanata CM

Homeostatic cytokines reciprocally modulate the emergence of prenatal effector PLZF+CD4+ T cells in humans.

JCI insight

Locher V, Park S, Bunis DG, Makredes S, Mayer M, Burt TD, Fragiadakis GK, Halkias J

Integrated longitudinal multi-omics study identifies immune programs associated with COVID-19 severity and mortality in 1152 hospitalized participants.

bioRxiv : the preprint server for biology

Gygi JP, Maguire C, Patel RK, Shinde P, Konstorum A, Shannon CP, Xu L, Hoch A, Jayavelu ND, Network I, Haddad EK, Reed EF, Kraft M, McComsey GA, Metcalf J, Ozonoff A, Esserman D, Cairns CB, Rouphael N, Bosinger SE, Kim-Schulze S, Krammer F, Rosen LB, van Bakel H, Wilson M, Eckalbar W, Maecker H, Langelier CR, Steen H, Altman MC, Montgomery RR, Levy O, Melamed E, Pulendran B, Diray-Arce J, Smolen KK, Fragiadakis GK, Becker PM, Augustine AD, Sekaly RP, Ehrlich LIR, Fourati S, Peters B, Kleinstein SH, Guan L

Cyclone: an accessible pipeline to analyze, evaluate, and optimize multiparametric cytometry data.

Frontiers in immunology

Patel RK, Jaszczak RG, Im K, Carey ND, Courau T, Bunis DG, Samad B, Avanesyan L, Chew NW, Stenske S, Jespersen JM, Publicover J, Edwards AW, Naser M, Rao AA, Lupin-Jimenez L, Krummel MF, Cooper S, Baron JL, Combes AJ, Fragiadakis GK

A myeloid program associated with COVID-19 severity is decreased by therapeutic blockade of IL-6 signaling.

iScience

Hackney JA, Shivram H, Vander Heiden J, Overall C, Orozco L, Gao X, Kim E, West N, Qamra A, Chang D, Chakrabarti A, Choy DF, Combes AJ, Courau T, Fragiadakis GK, Rao AA, Ray A, Tsui J, Hu K, Kuhn NF, Krummel MF, Erle DJ, Kangelaris K, Sarma A, Lyon Z, Calfee CS, Woodruff PG, Ghale R, Mick E, Byrne A, Zha BS, Langelier C, Hendrickson CM, van der Wijst MGP, Hartoularos GC, Grant T, Bueno R, Lee DS, Greenland JR, Sun Y, Perez R, Ogorodnikov A, Ward A, Ye CJ, UCSF COMET Consortium, Ramalingam T, McBride JM, Cai F, Teterina A, Bao M, Tsai L, Rosas IO, Regev A, Kapadia SB, Bauer RN, Rosenberger CM

Distinct pulmonary and systemic effects of dexamethasone in severe COVID-19.

Research square

Fragiadakis G, Neyton L, Patel R, Sarma A, Consortium UC, Willmore A, Haller SC, Kangelaris K, Eckalbar W, Erle D, Krummel M, Hendrickson C, Woodruff P, Langelier C, Calfee C

Single-Cell Multiomics.

Annual Review of Biomedical Data Science

Flynn E, Almonte-Loya A, Fragiadakis GK

Cyclone: an accessible pipeline to analyze, evaluate and optimize multiparametric cytometry data.

bioRxiv : the preprint server for biology

Patel RK, Jaszczak RG, Kwok I, Carey ND, Courau T, Bunis D, Samad B, Avanesyan L, Chew NW, Stenske S, Jespersen JM, Publicover J, Edwards A, Naser M, Rao AA, Lupin-Jimenez L, Krummel MF, Cooper S, Baron J, Combes AJ, Fragiadakis GK

SARS-CoV-2 infection of airway organoids reveals conserved use of Tetraspanin-8 by Ancestral, Delta, and Omicron variants.

Stem cell reports

Hysenaj L, Little S, Kulhanek K, Magnen M, Bahl K, Gbenedio OM, Prinz M, Rodriguez L, Andersen C, Rao AA, Shen A, Lone JC, Lupin-Jimenez LC, Bonser LR, Serwas NK, Mick E, Khalid MM, Taha TY, Kumar R, Li JZ, Ding VW, Matsumoto S, Maishan M, Sreekumar B, Simoneau C, Nazarenko I, Tomlinson MG, Khan K, von Gottberg A, Sigal A, Looney MR, Fragiadakis GK, Jablons DM, Langelier CR, Matthay M, Krummel M, Erle DJ, Combes AJ, Sil A, Ott M, Kratz JR, Roose JP

Randomized controlled trial demonstrates response to a probiotic intervention for metabolic syndrome that may correspond to diet.

Gut microbes

Wastyk HC, Perelman D, Topf M, Fragiadakis GK, Robinson JL, Sonnenburg JL, Gardner CD, Sonnenburg ED

Distinct factors associated with short-term and long-term weight loss induced by low-fat or low-carbohydrate diet intervention.

Cell reports. Medicine

Li X, Perelman D, Leong AK, Fragiadakis G, Gardner CD, Snyder MP

Bioinformatics Analysis of Publicly Available Single-Nuclei Transcriptomics Alzheimer's Disease Datasets Reveals APOE Genotype-Specific Changes Across Cell Types in Two Brain Regions.

Frontiers in aging neuroscience

Belonwu SA, Li Y, Bunis DG, Rao AA, Solsberg CW, Oskotsky T, Taubes AL, Grone B, Zalocusky KA, Fragiadakis GK, Huang Y, Sirota M

Variation of Immune Cell Responses in Humans Reveals Sex-Specific Coordinated Signaling Across Cell Types.

Frontiers in immunology

Fragiadakis GK, Bjornson-Hooper ZB, Madhireddy D, Sachs K, Chen H, McIlwain DR, Spitzer MH, Bendall SC, Nolan GP

A Comprehensive Atlas of Immunological Differences Between Humans, Mice, and Non-Human Primates.

Frontiers in immunology

Bjornson-Hooper ZB, Fragiadakis GK, Spitzer MH, Chen H, Madhireddy D, Hu K, Lundsten K, McIlwain DR, Nolan GP

Discovering dominant tumor immune archetypes in a pan-cancer census.

Cell

Combes AJ, Samad B, Tsui J, Chew NW, Yan P, Reeder GC, Kushnoor D, Shen A, Davidson B, Barczak AJ, Adkisson M, Edwards A, Naser M, Barry KC, Courau T, Hammoudi T, Argüello RJ, Rao AA, Olshen AB, Immunoprofiler Consortium, Cai C, Zhan J, Davis KC, Kelley RK, Chapman JS, Atreya CE, Patel A, Daud AI, Ha P, Diaz AA, Kratz JR, Collisson EA, Fragiadakis GK, Erle DJ, Boissonnas A, Asthana S, Chan V, Krummel MF

Sex-Stratified Single-Cell RNA-Seq Analysis Identifies Sex-Specific and Cell Type-Specific Transcriptional Responses in Alzheimer's Disease Across Two Brain Regions.

Molecular neurobiology

Belonwu SA, Li Y, Bunis D, Rao AA, Solsberg CW, Tang A, Fragiadakis GK, Dubal DB, Oskotsky T, Sirota M

Increased risk of severe clinical course of COVID-19 in carriers of HLA-C*04:01.

EClinicalMedicine

Weiner J, Suwalski P, Holtgrewe M, Rakitko A, Thibeault C, Müller M, Patriki D, Quedenau C, Krüger U, Ilinsky V, Popov I, Balnis J, Jaitovich A, Helbig ET, Lippert LJ, Stubbemann P, Real LM, Macías J, Pineda JA, Fernandez-Fuertes M, Wang X, Karadeniz Z, Saccomanno J, Doehn JM, Hübner RH, Hinzmann B, Salvo M, Blueher A, Siemann S, Jurisic S, Beer JH, Rutishauser J, Wiggli B, Schmid H, Danninger K, Binder R, Corman VM, Mühlemann B, Arjun Arkal R, Fragiadakis GK, Mick E, Comet C, Calfee CS, Erle DJ, Hendrickson CM, Kangelaris KN, Krummel MF, Woodruff PG, Langelier CR, Venkataramani U, García F, Zyla J, Drosten C, Alice B, Jones TC, Suttorp N, Witzenrath M, Hippenstiel S, Zemojtel T, Skurk C, Wolfgang P, Borodina T, Pa-Covid SG, Ripke S, Sander LE, Beule D, Landmesser U, Guettouche T, Kurth F, Heidecker B

Type I interferon autoantibodies are associated with systemic immune alterations in patients with COVID-19.

Science translational medicine

van der Wijst MGP, Vazquez SE, Hartoularos GC, Bastard P, Grant T, Bueno R, Lee DS, Greenland JR, Sun Y, Perez R, Ogorodnikov A, Ward A, Mann SA, Lynch KL, Yun C, Havlir DV, Chamie G, Marquez C, Greenhouse B, Lionakis MS, Norris PJ, Dumont LJ, Kelly K, Zhang P, Zhang Q, Gervais A, Le Voyer T, Whatley A, Si Y, Byrne A, Combes AJ, Rao AA, Song YS, Fragiadakis GK, Kangelaris K, Calfee CS, Erle DJ, Hendrickson C, Krummel MF, Woodruff PG, Langelier CR, Casanova JL, Derisi JL, Anderson MS, Ye CJ, UCSF COMET consortium

Inhibition of MET Signaling with Ficlatuzumab in Combination with Chemotherapy in Refractory AML: Clinical Outcomes and High-Dimensional Analysis.

Blood cancer discovery

Wang VE, Blaser BW, Patel RK, Behbehani GK, Rao AA, Durbin-Johnson B, Jiang T, Logan AC, Settles M, Mannis GN, Olin R, Damon LE, Martin TG, Sayre PH, Gaensler KM, McMahon E, Flanders M, Weinberg V, Ye CJ, Carbone DP, Munster PN, Fragiadakis GK, McCormick F, Andreadis C

Gut-microbiota-targeted diets modulate human immune status.

Cell

Wastyk HC, Fragiadakis GK, Perelman D, Dahan D, Merrill BD, Yu FB, Topf M, Gonzalez CG, Van Treuren W, Han S, Robinson JL, Elias JE, Sonnenburg ED, Gardner CD, Sonnenburg JL

SARS-CoV-2 infection studies in lung organoids identify TSPAN8 as novel mediator.

bioRxiv : the preprint server for biology

Hysenaj L, Little S, Kulhanek K, Gbenedio OM, Rodriguez L, Shen A, Lone JC, Lupin-Jimenez LC, Bonser LR, Serwas NK, Bahl K, Mick E, Li JZ, Ding VW, Matsumoto S, Maishan M, Simoneau C, Fragiadakis G, Jablons DM, Langelier CR, Matthay M, Ott M, Krummel M, Combes AJ, Sil A, Erle DJ, Kratz JR, Roose JP

Single cell transcriptome analysis defines heterogeneity of the murine pancreatic ductal tree.

eLife

Hendley AM, Rao AA, Leonhardt L, Ashe S, Smith JA, Giacometti S, Peng XL, Jiang H, Berrios D, Pawlak M, Li LY, Lee J, Collisson EA, Anderson MS, Fragiadakis GK, Yeh JJ, Chun JY, Kim GE, Weaver VM, Hebrok M

dittoSeq: Universal User-Friendly Single-Cell and Bulk RNA Sequencing Visualization Toolkit.

Bioinformatics (Oxford, England)

Bunis DG, Andrews J, Fragiadakis GK, Burt TD, Sirota M

Longitudinal single-cell epitope and RNA-sequencing reveals the immunological impact of type 1 interferon autoantibodies in critical COVID-19.

bioRxiv : the preprint server for biology

van der Wijst MGP, Vazquez SE, Hartoularos GC, Bastard P, Grant T, Bueno R, Lee DS, Greenland JR, Sun Y, Perez R, Ogorodnikov A, Ward A, Mann SA, Lynch KL, Yun C, Havlir DV, Chamie G, Marquez C, Greenhouse B, Lionakis MS, Norris PJ, Dumont LJ, Kelly K, Zhang P, Zhang Q, Gervais A, Voyer TL, Whatley A, Si Y, Byrne A, Combes AJ, Rao AA, Song YS, UCSF COMET consortium , Fragiadakis GK, Kangelaris K, Calfee CS, Erle DJ, Hendrickson C, Krummel MF, Woodruff PG, Langelier CR, Casanova JL, Derisi JL, Anderson MS, Ye CJ

A "data sharing trust" model for rapid, collaborative science.

Cell

Chan V, Gherardini PF, Krummel MF, Fragiadakis GK

Global absence and targeting of protective immune states in severe COVID-19.

Nature

Combes AJ, Courau T, Kuhn NF, Hu KH, Ray A, Chen WS, Chew NW, Cleary SJ, Kushnoor D, Reeder GC, Shen A, Tsui J, Hiam-Galvez KJ, Muñoz-Sandoval P, Zhu WS, Lee DS, Sun Y, You R, Magnen M, Rodriguez L, Im KW, Serwas NK, Leligdowicz A, Zamecnik CR, Loudermilk RP, Wilson MR, Ye CJ, Fragiadakis GK, Looney MR, Chan V, Ward A, Carrillo S

Landscape of coordinated immune responses to H1N1 challenge in humans.

The Journal of clinical investigation

Rahil Z, Leylek R, Schürch CM, Chen H, Bjornson-Hooper Z, Christensen SR, Gherardini PF, Bhate SS, Spitzer MH, Fragiadakis GK, Mukherjee N, Kim N, Jiang S, Yo J, Gaudilliere B, Affrime M, Bock B, Hensley SE, Idoyaga J, Aghaeepour N, Kim K, Nolan GP, McIlwain DR

Global Absence and Targeting of Protective Immune States in Severe COVID-19.

bioRxiv : the preprint server for biology

Combes AJ, Courau T, Kuhn NF, Hu KH, Ray A, Chen WS, Cleary SJ, Chew NW, Kushnoor D, Reeder GC, Shen A, Tsui J, Hiam-Galvez KJ, Muñoz-Sandoval P, Zhu WS, Lee DS, Sun Y, You R, Magnen M, Rodriguez L, Leligdowicz A, Zamecnik CR, Loudermilk RP, Wilson MR, Ye CJ, Fragiadakis GK, Looney MR, Chan V, Ward A, Carrillo S, Matthay M, Erle DJ, Woodruff PG, Langelier C, Kangelaris K, Hendrickson CM, Calfee C, Rao AA, Krummel MF

Global Absence and Targeting of Protective Immune States in Severe COVID-19.

Research square

Krummel M, Combes A, Courau T, Kuhn N, Hu K, Ray A, Chen W, Cleary S, Chew N, Kushnoor D, Reeder G, Shen A, Tsui J, Hiam K, Sandoval PM, Zhu W, Lee D, Sun Y, You R, Magnen M, Rodriguez L, Leligdowicz A, Zamecnik C, Loudermilk R, Wilson M, Ye C, Fragiadakis G, Looney M, Chan V, Ward A, Carrillo S, Matthay M, Erle D, Woodruff P, Langelier C, Kangelaris K, Hendrickson C, Calfee C, Rao A

Long-term dietary intervention reveals resilience of the gut microbiota despite changes in diet and weight.

The American journal of clinical nutrition

Fragiadakis GK, Wastyk HC, Robinson JL, Sonnenburg ED, Sonnenburg JL, Gardner CD

FLOW-MAP: a graph-based, force-directed layout algorithm for trajectory mapping in single-cell time course datasets.

Nature protocols

Ko ME, Williams CM, Fread KI, Goggin SM, Rustagi RS, Fragiadakis GK, Nolan GP, Zunder ER

Sex Differences in the Blood Transcriptome Identify Robust Changes in Immune Cell Proportions with Aging and Influenza Infection.

Cell reports

Bongen E, Lucian H, Khatri A, Fragiadakis GK, Bjornson ZB, Nolan GP, Utz PJ, Khatri P

Pursuing Human-Relevant Gut Microbiota-Immune Interactions.

Immunity

Spencer SP, Fragiadakis GK, Sonnenburg JL

GateFinder: projection-based gating strategy optimization for flow and mass cytometry.

Bioinformatics (Oxford, England)

Aghaeepour N, Simonds EF, Knapp DJHF, Bruggner RV, Sachs K, Culos A, Gherardini PF, Samusik N, Fragiadakis GK, Bendall SC, Gaudilliere B, Angst MS, Eaves CJ, Weiss WA, Fantl WJ, Nolan GP

Gut microbiome transition across a lifestyle gradient in Himalaya.

PLoS biology

Jha AR, Davenport ER, Gautam Y, Bhandari D, Tandukar S, Ng KM, Fragiadakis GK, Holmes S, Gautam GP, Leach J, Sherchand JB, Bustamante CD, Sonnenburg JL

Links between environment, diet, and the hunter-gatherer microbiome.

Gut microbes

Fragiadakis GK, Smits SA, Sonnenburg ED, Van Treuren W, Reid G, Knight R, Manjurano A, Changalucha J, Dominguez-Bello MG, Leach J, Sonnenburg JL

Multicenter Systems Analysis of Human Blood Reveals Immature Neutrophils in Males and During Pregnancy.

Journal of immunology (Baltimore, Md. : 1950)

Blazkova J, Gupta S, Liu Y, Gaudilliere B, Ganio EA, Bolen CR, Saar-Dover R, Fragiadakis GK, Angst MS, Hasni S, Aghaeepour N, Stevenson D, Baldwin N, Anguiano E, Chaussabel D, Altman MC, Kaplan MJ, Davis MM, Furman D

Expression of specific inflammasome gene modules stratifies older individuals into two extreme clinical and immunological states.

Nature medicine

Furman D, Chang J, Lartigue L, Bolen CR, Haddad F, Gaudilliere B, Ganio EA, Fragiadakis GK, Spitzer MH, Douchet I, Daburon S, Moreau JF, Nolan GP, Blanco P, Déchanet-Merville J, Dekker CL, Jojic V, Kuo CJ, Davis MM, Faustin B

Mapping the Fetomaternal Peripheral Immune System at Term Pregnancy.

Journal of immunology (Baltimore, Md. : 1950)

Fragiadakis GK, Baca QJ, Gherardini PF, Ganio EA, Gaudilliere DK, Tingle M, Lancero HL, McNeil LS, Spitzer MH, Wong RJ, Shaw GM, Darmstadt GL, Sylvester KG, Winn VD, Carvalho B, Lewis DB, Stevenson DK, Nolan GP, Aghaeepour N, Angst MS, Gaudilliere BL

Biosynthesis and Regulation of Sulfomenaquinone, a Metabolite Associated with Virulence in Mycobacterium tuberculosis.

ACS infectious diseases

Sogi KM, Holsclaw CM, Fragiadakis GK, Nomura DK, Leary JA, Bertozzi CR

In Reply.

Anesthesiology

Angst MS, Fragiadakis GK, Gaudillière B, Aghaeepour N, Nolan GP

Patient-specific Immune States before Surgery Are Strong Correlates of Surgical Recovery.

Anesthesiology

Fragiadakis GK, Gaudillière B, Ganio EA, Aghaeepour N, Tingle M, Nolan GP, Angst MS

The effect of microbial colonization on the host proteome varies by gastrointestinal location.

The ISME journal

Lichtman JS, Alsentzer E, Jaffe M, Sprockett D, Masutani E, Ikwa E, Fragiadakis GK, Clifford D, Huang BE, Sonnenburg JL, Huang KC, Elias JE

Implementing Mass Cytometry at the Bedside to Study the Immunological Basis of Human Diseases: Distinctive Immune Features in Patients with a History of Term or Preterm Birth.

Cytometry. Part A : the journal of the International Society for Analytical Cytology

Gaudillière B, Ganio EA, Tingle M, Lancero HL, Fragiadakis GK, Baca QJ, Aghaeepour N, Wong RJ, Quaintance C, El-Sayed YY, Shaw GM, Lewis DB, Stevenson DK, Nolan GP, Angst MS

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Gabriela Fragiadakis, PhD